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Biomedical subjects

J C Kim

Publications and source records attributed to J C Kim.

At least 199 records · Page 11Linked to original sources

Collection of leukocytes, fibroblasts, and collagen within an implantable reservoir tube during tissue repair.

An implantable chamber consisting of a small reservoir and a perforated segment of silicone tubing has been developed for the collection of leukocytes, fibroblasts, and collagen to analyze inflammatory components and fibroplasia during tissue repair. Using aseptic techniques, these sterile chambers were placed into subcutaneous pockets on the backs of Sprague-Dawley rats with cells obtained in daily aspirates for 14 d. Differential cell counts were made by using aliquots from the wound fluid. The aspirated cells represented the characteristic, sequential influx of neutrophils, inflammatory macrophages, lymphocytes, activated macrophages, and fibroblasts documented in other models of tissue repair. On d 14, the connective tissue within the lumen of the silicone tube was removed and analyzed for collagen synthesis by measuring 3H-proline incorporation into collagenase-sensitive protein. This new device for studying wound healing provides a convenient means to harvest cells, fluid, and tissue for cellular, humoral, and biochemical analyses of tissue repair.

Animals↗

Acute toxicity in the guinea pig and in vitro "dioxin-like" activity of the environmental contaminant 1,2,4,5,7,8-hexachloro (9H)xanthene.

A number of sites in the state of Missouri have been contaminated with polychlorinated dibenzodioxins and dibenzofurans as a result of improper waste-oil application for dust control. In addition to these compounds, relatively high levels of 1,2,4,5,7,8-hexachloro(9H)xanthene (1,2,4,5,7,8-HCX), a by-product of hexachlorophene manufacture, were also detected. Unlike the dibenzodioxins and dibenzofurans, no animal toxicity data are available on the chlorinated xanthenes. In view of the potential importance of this novel class of environmental contaminants, studies were conducted to examine the acute oral toxicity in guinea pigs and in vitro "dioxin-like" activity of 1,2,4,5,7,8-HCX. Animals administered a single oral dose of 0.02, 0.1, 0.5 or 2.5 mg 1,2,4,5,7,8-HCX/kg in corn oil and sacrificed 42 d later exhibited no treatment-related pathology. Guinea pigs given 12.5 mg/kg displayed mild to moderate distension and histologically observable subserosal edema of the urinary bladder, in addition to mild fatty vacuolization of pancreatic acinar cells. The alterations were considered to be of minimal toxicological significance. No compound- or dose-related mortality, body weight loss, or organ weight changes were noted at any dose level. Results using an in vitro bioassay for "dioxin-like" activity confirmed preliminary data suggesting that 1,2,4,5,7,8-HCX is about 10(6) times less potent than 2,3,7,8-tetrachlorodibenzo-p-dioxin (2,3,7,8-TCDD) in this assay system. These findings indicate that 1,2,4,5,7,8-HCX may represent a relatively low environmental hazard compared to 2,3,7,8-TCDD.

Animals↗

2,2,2-Trifluoroethanol-induced enteropathy in rats: chemically or bacterially mediated effects.

The lethal effects of the fluorinated ether anesthetic, fluroxene, in rats are a consequence of its metabolism, which is catalyzed by cytochrome P-450 to the toxic metabolite 2,2,2-trifluoroethanol (TFE). The anesthetic or TFE (0.21 g/kg) caused decreased white blood cell counts, necrosis of bone marrow and lymphocytes, and decreased small intestine dry weight and was associated with septicemia. To elucidate the mechanism of TFE toxicity in rats we undertook histopathologic, ultrastructural and bacteriologic studies. TFE produced severe edema of intestinal lamina propria and submucosae, dilatation of crypts, loss of surface epithelium, vacuolation and necrosis of intestinal epithelial cells, and infiltration of polymorphonuclear leukocytes into the edematous lamina propria. Intestinal epithelial villi lost their cellular tissue integrity. Coccobacillary organisms were numerous in the ulcerated intestine. Hemolytic E. coli were isolated from intestinal tissue at a two-log increase in concentration relative to controls. Hemograms from TFE-treated rats exhibited marked leukopenia and morphologic differences. The platelets lost their discoid shape, extended pseudopods, and centralizing granules. Hemoglobin precipitation as Heinz bodies and crystalloid structures was observed in TFE-treated rats. Together the data suggest that TFE-induced enteropathy was most probably due to E. coli precipitated from TFE-mediated alterations in the population of small intestinal microbes. The antibiotics erythromycin, active against gram-positive bacteria, and streptomycin, active against gram-negative bacteria, and the antiendotoxin, polymyxin B, were administered to rats prior to TFE in an effort to differentiate between these mechanisms by altering the intestinal bacteria populations. The results indicate that the TFE-induced small intestinal lesions are initiated by the direct focal necrotic effect of TFE or its metabolites on the small intestinal epithelium. The focal coagulation necrosis produced by TFE predisposes the animals to lethal enteritis and systemic bacteremia.

Animals↗

2,2,2-Trifluoroethanol toxicity in hamsters (Mesocricetus auratus).

As part of an effort to further elucidate the mechanism whereby fluorinated ether anesthetics express their various toxic effects, Golden Syrian hamsters were utilized to determine acute and subchronic toxicities of the anesthetic metabolite 2,2,2-trifluoroethanol (TFE). The major lesion observed with the TFE (0.25 g/kg ip) was coagulation necrosis characterized by nuclear pyknosis in epithelial cells of intestinal villi, the deeper portion of gastric mucosae, lymphoid organs such as thymus, spleen and mesenteric lymph nodules and brain. Hepatocyte hypertrophy with diffuse vacuolar degeneration was also found. Lungs had a characteristic focal terminal bronchiolar epithelial hyperplasia with discrete mucous metaplasia in the terminal bronchioles. In subchronic studies, hamsters were injected with sublethal doses of TFE (0.20 g/kg once per week for 5 weeks). The major lesions observed were severe hepatocyte hyperplasia and hypertrophy with fatty degeneration, necrosis of hair germinal matrix, urinary bladder transitional epithelial cellular hypertrophy, and hyperplasia with vacuolar degeneration and submucosal edema. Ultrastructural studies of acutely treated animals indicate that fat vacuoles formed within the hepatic endoplasmic reticulum characterized by lamellar bodies forming multiple myelin figures within the fat vacuoles. Hepatic cytochrome P-450 concentrations measured as a possible index of endoplasmic reticulum damage, failed to reveal any significant differences between the treated and non-treated hamsters.

Animals↗

Ultrastructural and microprobe analysis of simian lung mite pigments.

Using light microscopy, polarizable amorphorous bodies with tinctorial characteristics of lipochromes and flocculent pigmental materials were found within the alveolar macrophages and peribronchiolar region of the lungs in a pig-tailed macaque (Macaca nemistrina) infected with simian lung mite (Pneumonyssus simicola). Examination of these pigmental bodies, using a high-voltage (1.2 meV) electron microscope and an energy-dispersive X-ray analysis system, indicated that the pigmental bodies contained a high concentration of silica. One female adult P simicola also was examined, and its digestive tract had visible, polarizable pigment and a high concentration of silica. Thus, lesions associated with lung mite infection in Old World monkeys may be superimposed by this silicotic condition, which may be associated with their arid, dusty, environment. Therefore, until the link between lung mite infection and silicosis is clarified, experimental inhalation toxicologic findings in mite-infected Old World monkeys should be interpreted cautiously.

Animals↗

Acute leukemic infiltration of the prostate. Successful treatment with radiation.

Infiltration of the prostate by acute granulocytic leukemia can cause diagnostic and therapeutic difficulties. After stabilization of hematologic findings, the diagnosis can be made safely by needle biopsy of the prostate. The prostate may be one of the so-called sanctuary areas where chemotherapy does not affect the leukemic infiltrate. This process may be a source of reactivation of leukemia in patients who had achieved a hematologic remission. This report describes a patient who had successful eradication of acute myelomonocytic leukemia from the prostate by radiation therapy while in hematologic remission. Better surveillance for leukemic infiltrate of the prostate is needed, including needle biopsy when appropriate. Radiation may be an effective therapy for this manifestation of leukemia.

Adult↗

Clinical results of early stage prostatic cancer treated by pelvic lymphadenectomy and 125iodine implants.

Eighty patients with clinically early stage adenocarcinoma of the prostate were treated with pelvic lymphadenectomy and interstitial implantation of 125iodine seeds. A new applicator that permits greater accuracy in spacing the seeds has been developed. Postoperative complications were minimal, with urinary irritability being the most common. Multiple transrectal needle biopsies were performed 12 and 18 months after treatment in 46 patients. The prostatic biopsies were negative for carcinoma in 61 per cent and positive in 39 per cent of the patients. Long-term followup is needed to correlate post-treatment biopsies with survival and to determine if patients with positive biopsies should receive further treatment.

Aged↗

The prostate of the nonhuman primate: normal anatomy and pathology.

The caudal and cranial prostate of different species of nonhuman primates were examined for histologic characteristics and pathological abnormalities. One hundred specimens from 12 species were represented. Among the pathologies found were: 1) cystic hyperplasia; 2) fibromuscular hyperplasia; 3) squamous metaplasia; 4) chronic and acute bacterial prostatitis; 5) prostate adenocarcinoma; and 6) other miscellaneous pathologic changes. A historical review of histological characteristics and pathological abnormalities of the nonhuman primate prostate is given. Based upon findings in this study, anatomical similarity of the caudal lobe of the prostate to the peripheral zone of the prostate in humans as described by McNeal is found. In the patas monkey the relationship of the cranial and caudal lobe suggests strongly the relationship seen between the central and peripheral zones in man. The case of prostatic adenocarcinoma described has only been reported in one other nonhuman primate.

Animals↗

Immunology of pyelonephritis in the primate model: live versus heat-killed bacteria.

We produced nonobstructive pyelonephritis in the rhesus monkey (Macaca mulatta) by means of a retrograde inoculation of Escherichia coli to the point of pyelotubular backflow. To evaluate the immune response separate from the effects of infection, we introduced heat-killed bacteria in the same fashion. The disease from live bacteria is self-limited and associated with both a local and generalized immune response. The most marked cellular response is in the regional lymph nodes and is more specific to the bacterial antigen than is generalized stimulation of the immune system. Dead bacteria, while eliciting the formation of serum antibody to the O antigen, appear to ablate the cellular response seen with live bacteria. Loss of renal tubules with attended scarring and loss of renal function does occur from live bacteria. This does not appear to be due to the antigen alone (unless a heat labile antigen is responsible), because heat-killed bacteria do not cause renal scarring. Thus, renal damage seems dependent on an active infection and not on the immune response.

Animals↗

Immunology of pyelonephritis in the primate model. II. Effect on immunosuppression.

Nonobstructive pyelonephritis was produced in the rhesus monkey (Macaca mulatta) by means of retrograde inoculation of Escherichia coli to the point of pyelotubular backflow. The effects of treatment with cyclophosphamide or azathioprine were determined. Commensal renal viruses were not activated by the immunosuppression, and thus did not complicate our results. Both cyclophosphamide and azathioprine prolonged the bacteriuria and produced more severe pathology. Cyclophosphamide decreased the leukocytic response and partically suppressed the antibody response. The increased amount of acute pyelonecytic response and partially suppressed the antibody response. The increased amount of acute pyelonephritic lesions after treatment with this drug suggest that the antibody and inflammatory responses may be important protective mechanisms, particularly regarding prevention of abscesses. In contrast, azathioprine did not decrease the leukocytosis nor the antibody responses, but resulted in decreased in vitro responsiveness of lymphocytes to mitogens. The increased severity of chronic pyelonephritic lesions after azathioprine treatment suggests that the cellular immune response also may be an important protective mechanism during late stages of the disease. The results thus indicate that the immune response is protective and is not directly responsible for the chronic scarring of pyelonephritis.

Animals↗

Late effects of para-aortic irradiation in carcinoma of the uterine cervix and endometrium.

Twenty-one patients with cervical or endometrial carcinoma and metastases to the para-aortic lymph nodes were treated with extended-field para-aortic irradiation. The late effects of this treatment were evaluated in 16 patients who had a minimum follow-up of six months. All of the patients with massive pelvic tumours died of active disease in the pelvis with or without metastases. Three patients had small-bowel complications; none of the patients who underwent exploratory laparotomy for lymph node biospy had bowel complications. The results indicate that patients with central lesions and minimal para-aortic disease benefit most from para-aortic irradiation. It is concluded that metastases to the para-aortic lymoh nodes do not necessarily indicate more distant spread, and can be cured with irradiation. The late complication rate can be minimized by reducing the dosage to the small bowel with a combination of anterior-posterior fields and 360 degree rotation or opposing lateral 120 degree arc fields, and by using the extraperitoneal approach for lymph node biopsy.

Abdomen↗

Vitamin A and the susceptibility of respiratory tract tissues to carcinogenic insult.

The influence of vitamin A on the development of chemically induced lung carcinomas in rats was investigated. Rats were maintained on low, "normal" and excess levels of retinyl acetate (RA). Respiratory tract-squamous carcinomas were induced by intratracheal injections of 3-methylcholanthrene (3-MCA). The carcinogen doses used ranged from 1.25 to 10.0 mg of 3-MCA. Serial sacrifices conducted during the first 20 weeks following carcinogen exposure showed that metaplastic lung nodules, presumed to be precursors of later appearing carcinomas, occurred earlier and at higher incidence in rats maintained on low levels of RA than in rats maintained on moderate or high levels of RA. The development of invasive pulmonary carcinomas was enhanced at all four carcinogen doses in rats receiving low levels of RA as compared to rats receiving moderate or high levels of RA. No consistent difference in lung cancer incidence existed between the groups receiving normal and high levels of RA. The data clearly show an increased susceptibility of vitamin A-deficient rats to develop chemically induced lung cancers. Possible mechanisms underlying this effect are discussed.

Animals↗

Carcinoma of the vocal cord: results of treatment and time-dose relationships.

A retrospective analysis has been done of 173 patients with epidermoid carcinoma of the vocal cord treated with radiation therapy at Rush-Presbyterian-St. Luke's Medical Center between January 1970 and December )974. one hundred fifty-eight patients (91.3%) were early (T1, T2) glottic lesion and 10 were advanced (T3, T4) lesion. Five (2.9%) were presented with positive cervical lymph nodes initially. Of 158 patients who had T1, T2N0M0 glottic tumor, 146 had definitive radiation therapy and 12 had preoperative radiation therapy. An analysis of frequency of local recurrence versus total dose (NSD) has been done for 146 patients and a dose response curve has been generated. Local failure rates were 22.2% for 1,800 +/- 50 rets, 11.1% for 1,900 +/- 50 rets, and 3.2% for 2,000 +/- 50 rets. For the early glottic cancer, local control rates were increased with increasing total dose without significant complications. In patients with advanced primary tumors, a greater number of the patients were treated with preoperative radiation therapy and this group had slightly better results.

Adult↗

The effect of dietary vitamin A on NO2 exposure on the hamster lung.

The effect of dietary vitamin A and NO2 exposure on the hamster lung was evaluated by histopathology, electron microscopy, and thymidine uptake studies. Hamsters were maintained on deficient (0 micrograms), adequate (100 micrograms), and high (200 micrograms) dose levels of vitamin A while being exposed repeatedly to 10 ppm of NO2 for 5 hours once a week over an 8-week period. Hamsters of the deficient group exhibited clinical and morphologic changes characteristic of vitamin A deficiency. Animals maintained on adequate and high dose levels of vitamin A were not affected by vitamin A deficiency. Hypertrophy and hyperplasia of the epithelial cells of the terminal bronchiolar alveolar region of lungs of adequately and highly dosed animals were greater than those observed in the deficient animals, when NO2 exposure was given. However, the extent of the lesions observed in all three groups was less than that seen in normal hamsters given a single, 5-hour NO2 exposure. Ultrastructural changes observed in vitamin A-deficient hamsters exposed to NO2 were hypertrophy and hyperplasia of bronchiolar epithelial cells, diffuse loss of cilia, membrane damage, and mitochondrial damage manifested by calcium deposition. Tritiated thymidine uptake studies of lungs of animals exposed repeatedly revealed a rather erratic cell renewal pattern following NO2 exposure in comparison to the group of animals exposed singly.

Animals↗